Environmental tobacco smoke (ETS), also known as second-hand or passive smoke exposure, affects approximately 15 million youth under the age of 18, and results in numerous acute and chronic illnesses. Approximately 45,000-60,000 adult nonsmokers die annually from cardiovascular disease (CVO) as a result of ETS exposure. Cotinine, a metabolite of nicotine, is frequently used as a physiological measure of ETS exposure. Several studies have reported that cotinine is metabolized at a different rate in males than in females and in African Americans (AA) than in European Americans (EA). The reason for this difference has not been determined and may be related to genetic variations/polymorphisms involved in metabolizing nicotine and in the biotransformation of tobacco smoke. Specific candidate genes involved in these biotransformation reactions include CYP1A1, GSTM1, GSTT1, and CYP2A6. The development of CVD is multifactorial and gene- environment interactions between specific nicotine metabolizing genes and ETS exposure may provide new information regarding the development of pre-clinical CVD risk factors in youth. The primary pre-clinical CVD risk factor measured in this project is resting systolic blood pressure (SBP) and secondary phenotypes include resting diastolic blood pressure (DBP), endothelium-dependent arterial vasodilation (EDAD), left ventricular mass indexed by body size (LVMI), and total peripheral resistance (TPR). Currently, the relationship between genetics, exposure to ETS and the development of pre-clinical CVD risk factors in youth is not understood. Exploring such relationships particularly within the context of gene-environment interactions may provide information for identifying youth at increased risk for developing CVD. This project is a secondary analysis (N=585) of data that have been collected by Dr. Frank Treiber (Co-l) (HL69999). There has been no prior evaluation during his funded research of the relationships proposed in this application. Frozen plasma and DMA are available for performing cotinine analyses and genotyping and all dependent CV measures are in the established database. This application, consistent with the mission of the National Institute of Nursing Research, targets three priority areas for the R15 application to include cultural and ethnic considerations in health, health promotion and disease prevention, and new knowledge of implications for genetic advances. This research addresses a significant public health concern for ETS exposed youth. Examining the combined impact of genetics and ETS exposure may provide information to develop socio-culturally appropriate interventions for preventing CVD in youth who are identified at increased risk based on their genetics and at-risk environments. [unreadable] [unreadable] [unreadable] [unreadable]